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Biomedical subjects

C Holmberg

Publications and source records attributed to C Holmberg.

At least 163 records · Page 9Linked to original sources

Na to Cl permeability in newborn rabbit superficial and juxtamedullary proximal convoluted tubules.

It has been previously demonstrated that superficial (SF) versus juxtamedullary (JM) proximal convoluted tubules (PCT) of rabbit have different intrinsic transport characteristics: Na is less permeable than Cl in the latter portions of the SFPCT, while Cl is less permeable than Na throughout the JMPCT. These permeability differences have major influences on the mechanism of salt reabsorption across the proximal tubules. However, both populations of PCT have the same embryological origin. Studies therefore were designed to examine whether two distinct populations of PCT exist at birth or whether a second population of tubules develops with delivery as a result of some unidentified acute change in humoral factor affecting epithelial transport properties. Both morphological and electrophysiological studies were conducted on PCTs from rabbits within 36 h of birth. Both transmission and scanning electron microscopy studies clearly disclosed that SFPCT are less mature than the JMPCT. Also the SFPCT had a lower Na permeability than Cl (0.55 +/- 0.06) while the JMPCT had a higher Na permeability than Cl (1.37 +/- 0.11). Thus these studies demonstrate that intrinsic heterogeneity of PCT is present at birth. Since the SF Na to Cl permeability approximates that of free diffusion these studies suggest that epithelial discrimination in PCT is part of a maturation process.

Animals↗

Interdisciplinary teaching of community paediatrics.

An experiment of combining decentralized and interdisciplinary teaching is described. Seminars were arranged at a district hospital for medical, nursing and social work students to discuss families with a chronically ill child. The purpose of these seminars was to teach co-operation between different health care workers, and to stress the importance of becoming acquainted with the family situation, and learn what a child's illness means to the whole family. An evaluation of the first three seminars shows that this type of teaching was very well received by the students, professionals and families concerned. The students considered house calls an important part of their education and felt that more interdisciplinary teaching should be included in their curriculum. In addition to the teaching aspect, the families involved also considered the seminars a positive experience as they receive more information about their child's disease, and deficiencies in treatment could be corrected.

Attitude to Health↗

Lack of solvent drag of NaCl and NaHCO3 in rabbit proximal tubules.

Using in vitro microperfusion of rabbit nephron segments we measured the effects of osmotically induced water flow on net transport of HCO3 and Cl. Measurements were made in superficial and juxtamedullary proximal convolutions and in superficial pars recta. In addition, measurements were taken in the presence and absence (hypothermia) of active transport. Using osmotic gradients of 25 mM raffinose in superficial and 50 mM in juxtamedullary segments, we observed increases in water flow equal to or greater than the normal rates of volume reabsorption observed in these tubule segments. However, there were no significant changes in HCO3 and Cl flux. This lack of significant solvent drag was seen both when osmotic water flow was in the lumen-to-bath direction and when osmotic flow was in the bath-to-lumen direction. The results of these studies suggest that solvent drag does not contribute significantly to NaCl and NaHCO3 reabsorption in proximal tubules. The lack of significant solvent drag of these salts can be interpreted as indicating either that osmotically induced transepithelial water flow in proximal tubules almost exclusively traverses transcellular pathways or that proximal tubule tight junction reflection coefficients for these salts are close to unity.

Animals↗

Determination of chloride and bicarbonate permeabilities in proximal convoluted tubules.

In late proximal tubules volume reabsorption linked to passive ion flows relies on the existence of differing permeability coefficients to Cl- and HCO3(-) (PCl greater than PHCO3). We measured these permeability coefficients in late segments of rabbit superficial (SFPCT) and juxtamedullary (JMPCT) proximal convoluted tubules perfused in vitro. PHCO3 and P36Cl were determined in tubules bathed in rabbit serum and perfused with a serum ultrafiltrated titrated with H2SO4 to [HCO3(-)] of 4 mM. Active transport, transepithelial voltage, and HCO3(-) reabsorption were inhibited by cooling (21 degrees C) and 10(-4) M acetazolamide. P36Cl and PHCO3 were calculated from 36Cl disappearance from and total CO2 addition to the perfusate. P36Cl in SFPCT was twice that in JMPCT but PHCO3 was the same in both segments. P36Cl exceeded PHCO3 only in SFPCT. To exclude exchange diffusion from contributing to P36Cl, additional tubules were perfused with ultrafiltrate titrated with HCl.P36Cl and simultaneously measured PCl (lumen-to-bath net chemical Cl- flux) were identical. We conclude: 1) SFPCT and JMPCT are heterogeneous with respect to Cl- permeability; 2) relative Cl--to-HCO3(-) permeabilities predict that anion gradients present in late portions of proximal tubules would support more volume reabsorption linked to passive ion flows in SF than in JMPCT; 3) no significant Cl- exchange diffusion exists in proximal tubules.

Absorption↗

Oncogenicity of gibbon type-C myelogenous leukemia virus.

Young gibbons that were experimentally inoculated with cell-free gibbon ape leukemia virus (GaLV) and developed peristent viremia subsequently developed chronic granulocytic leukemia (CGL) with associated multifocal bone lesions and metastases. An 8-month-old gibbon inoculated with 10(5) tissue culture infectious virus (TCIV) developed acute myeloproliferative disease with associated bone lesions after a latency of 5 months, while a 9-month-old gibbon inoculated with 10(3) TCIV developed CGL after and 11-month latency. The clinical symptoms associated with the onset of leukemia were an increased number of leukocytes which were predominantly mature granulocytes, development of anemia, and multifocal bone lesions. Terminally, the animals had elevated immature granulocytes in the blood, cellular bone marrow with a predominant number of immature granulocytes, and hepatosplenomegaly. The gibbon with CGL had metastatic growth in the spleen and lung. Two 14-month-old gibbons that were inoculated with 10(3) TCIV and developed persistent neutralizing antibody to the virus infection remained free of hematopoietic disease, as did uninoculated animals. The fact that only animals with persistent viremia developed leukemia supports the oncogenicity of GaLV in gibbons.

Animals↗

The incidence of coccidioidomycosis among nonhuman primates housed outdoors at the California Primate Research Center.

Serum from 191 nonhuman primates housed outdoors from October 1977 to October 1978 at the California Primate Research Center was assayed for the presence of antibody specific for coccidioidin. One Macaca mulatta had coccidioidal antibody which was found to be associated with disseminated coccidioidomycosis. One Macaca radiata had complement-fixing antibody specific for coccidioidin and a pulmonary lesion. Additionally, two other animals had coccidioidal antibody but lacked clinical evidence of disease. The source of infection is suspected to be a severe dust storm originating in southern California.

Animals↗

Electrolyte economy and its hormonal regulation in congenital chloride diarrhea.

The economy of Cl-, K+, and Mg++, extracellular volume (ECV) and plasma volume, and the role of hyperreninemia and hyperaldosteronism were explored in 22 patients with congenital chloride diarrhea. Stool volume was in significant correlation with its Cl-, Na+ and K+ content, the correlation being significantly better with Cl- content than with the Na+ content. Low fecal Cl- concentrations were seen in chronic hypochloremic contraction, but acute episodes did not cause reduction of fecal Cl- concentration from the basal level of 140--150 mmol/liter. The adequate condition (defined as normal serum electrolyte concentrations and bl;od pH, and presence of Cl- in urine) was associated with high total exchangeable Cl- and ECV. This excess Cl- and ECV roughly equalled the high daily fecal amount of Cl- and volume. Reduced ECV was accompanied by high renin activities and hyperaldosteronism, but in the adequate condition these were normal. Hyperaldosteronism caused a decrease in urinary Na+-K+ ratio and, after the age of 2--6 months, in the fecal Na+-K+ ratio. Total exchangeable K+ was normal in the adequate condition. No Mg++ depletion was present, although the patients lack Mg++ substitution. The adequate condition could be maintained with an oral supplement of NaCl, KCl and water.

Adolescent↗

The renal lesion in congenital chloride diarrhea.

Congenital chloride diarrhea is an inherited defect of active intestinal Cl- transport which results in a large wastage of electrolytes and water. The effects of this disease and of replacement therapy on renal histology, function, growth, and the renin-angiotensin-aldosterone system were studied in 18 patients. When the patients were given KCl supplement, histologic findings included juxtaglomerular hyperplasia hyalinized glomeruli, calcifications, and arteriolar changes. Renal function and growth were reduced, and the hormonal activities were high. These abnormalities were evidently due to chronic dehydration. The dehydration could be corrected by increasing the dose of KCl, but only the addition of NaCl corrected the hyperaldosteronism. Adequate replacement therapy prevented the renal involvement.

Child↗

Congenital chloride diarrhoea. Clinical analysis of 21 Finnish patients.

Clinical findings in 21 Finnish children with congenital chloride diarrhoea are reported. Inheritance of this disease by the autosomal recessive mode is established. All children were born 1-8 weeks prematurely. Hydramnios was present in every case and no meconium was observed; intrauterine onset of diarrhoea is thus apparent. In most cases the diarrhoea or passing of large volumes of "urine" was noted on the first day of life and the abdomen was usually large and distended. The neonatla weight loss was abnormally large, and was associated with hypochloraemia and hyponatraemia. Some infants survived the neonatal period without adequate therapy. They presented later with failure to thrive and usually had hypochloraemia, hypokalaemia, and metabolic alkalosis associated with hyperaldosteronism. However, these features may be absent and the diagnosis is based on a history of hydramnios and diarrhoea, and a faecal Cl- concentration which always exceeds 90 mmol/l when fluid and electrolyte deficits have been corrected. Lower faecal Cl- concentrations were seen only in chronic hypochloraemia, which is also associated with achloriduria. Adequate treatment consists of full continuous replacement of the faecal losses of water, NaCl, and KCl. This should be given intravenously in the early neonatal period; later a solution can be taken orally with meals. The dose has to be adjusted to maintain normal serum electrolyte concentrations, normal blood pH, and some chloriduria. This therapy prevents the renal lesions and the retarded growth and psychomotor development which were seen in the children who were diagnosed late and in those who received inadequate replacement therapy. The watery diarrhoea persists and increases slightly with age, though patients learn to live with their disease and to make an adequate social adjustment.

Abdomen↗

Inappropriate secretion of antiduretic hormone, hypertension, and hypoplastic corpus callosum.

The threshold of serum osmolality causing release of vasopressin (antidiuretic hormone) was shifted to an abnormally low level (262 mosmol/kg H2O) in a 14-year-old girl with hypertension and signs of hypoplastic corpus callosum. There was a physiologically meaningful control of vasopressin release in response to water restriction and water load. Plasma vasopressin concentrations (range 1.2--11.9 pg/ml) were of the same magnitude as those of healthy adults, being abnormally high only when related to the hypotonicity of serum observed. Plasma concentrations of angiotensin II were higher than expected from the suppressed levels of plasma renin activity. Blood-pressure response to angiotensin II infusion was increased. Resetting of the osmostat and hypertension may both be explained by lesions of the central nervous system.

Adolescent↗

Mycobacterium avium infection in three rhesus monkeys.

Naturally occurring Mycobacterium avium infection in 3 rhesus monkeys was characterized clinically and pathologically by intestinal and lymphoreticular involvement. Blood lymphocyte rosette formation and phytomitogen responses were depressed, whereas serum beta and gamma globulin concentrations were increased. Slow-growing, acid-fast, nonchromogenic bacilli isolated from lymph nodes taken at necropsy were identified as M avium serotypes 4, 18, and double types 1 and 8.

Animals↗

Colonic electrolyte transport in health and in congenital chloride diarrhea.

Congenital chloride diarrhea (CCD) is a rare autosomal recessive disorder, characterized by watery stools with C1- concentration around 150 meq/liter. We have perfused the colon of three patients and their three healthy siblings with different salt solutions containing 36C1- to determine the nature of the colonic defect in CCD. In the controls, net absorption of Na+ and C1- occurred against steep concentration gradients. The influx (lumen-to-plasms flux) of C1- was twice the effux. Omission of HCO3- from the perfusate caused a clear decrease in C1- efflux which suggests a coupling of C1- effux to HCO3- influx. In CCD, net Na+ absorption occurred normally when HCO3- was present in the lumen. However, Na+ absorption was always impaired when the luminal contents were acid, a situation that prevails in CCD. Net K+ secretion was clearly increased. Both influx and efflux of C1- were practically absent. Only slight net secretion occurred along a steep gradient. Net appearance of HCO3- was not observed, in contrast to controls. These findings and earlier studies of ileal function in CCD are best explained by a defect in the C1-/HCO3- exchange mechanism, which operates in both directions in the normal ileum and colon.

Bicarbonates↗

Alpha-actinin and myosin light chains in congenital nemaline myopathy.

The muscle fibers of patients with congenital nemaline myopathy contain nemaline bodies, of which alpha-actinin is a major constituent. In some cases, deficiencies of fast myosin light chains have been reported. We performed 1-dimensional polyacrylamide sodium dodecyl sulfate gradient gel electrophoresis of muscle proteins from 13 patients with congenital nemaline myopathy and 10 controls to examine the alpha-actinin and the distribution of myosin light chains in congenital nemaline myopathy. At 95 kd (corresponding to alpha-actinin), 4 patients and all controls had 1 band, 2 patients did not have any bands, and 7 had bands that were clearly weaker than those of the controls. Because alpha-actinin is present in the nemaline bodies of congenital nemaline myopathy muscle, only the deficiency of this protein must be apparent. No apparent differences in fast myosin light-chain distribution could be documented between patients and controls; no correlation was observed between muscle fiber type and light-chain distribution. The results suggest that alpha-actinin is abnormal in congenital nemaline myopathy.

Actinin↗

Ultrasonography, CT, and MRI of muscles in congenital nemaline myopathy.

Twelve patients with congenital nemaline myopathy were examined by ultrasonography and computed tomography (CT) and 4 of them by low-field magnetic resonance imaging (MRI) to investigate the distribution and nature of muscle involvement and to evaluate the yield of these techniques. A pattern of selective muscle involvement was consistently found. Ultrasonography revealed abnormally high muscle echogenicity. In contrast to the controls with simple disuse and/or neurogenic atrophy, CT revealed low muscle density in our patients. MRI confirmed that this pattern reflects patchy, fatty degeneration, a new finding in congenital nemaline myopathy. Ultrasonography appears useful for screening, provided that the dorsiflexors of the feet are examined. CT and MRI can be used to demonstrate abnormalities in mild cases, to select the biopsy site, and for follow-up. MRI, because it provides good soft tissue contrast, is useful for determining fatty infiltration.

Adolescent↗